4-Chloro-3-iodopyridin-2-amine → 7-Chloro-8-iodo-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine

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Reaction Conditions

Reaction Steps

A 2.0-5.0 mL microwave vial was charged with 2-bromo-4,4,4-trifluorobutanal (403 mg, 1.965 mmol) dissolved in EtOH (2500 μl). To that stirring solution was added 4-chloro-3-iodopyridin-2-amine (250 mg, 0.982 mmol). The vial was sealed and heated in the microwave for 1 h at 150° C. After 1 hour, LCMS showed clean and complete consumption of the starting material to a single peak with the desired mass (m/z=260 [M+H]+; Methanol/Water/TFA Phenomenex Luna C18, 30×2 mm, 3u ES+/−). The mixture was transferred into a round bottom flask and the ethanol was removed under reduced pressure. The crude mixture was diluted with EtOAc and sat'd sodium bicarbonate. The contents of the flask were transferred into a separatory funnel where the aqueous was extracted twice with EtOAc and discarded. The combined organics were washed with brine, dried with magnesium sulfate, concentrated under reduced pressure, and purified by flash chromatography: (25 g, equilibrated with hexanes, loaded with DCM, initial waste: mL, fraction size: 9 mL 13×100 mm, and eluted with EtOAc in hexanes 0% [115 mL], 10% [150 mL], 20% [400 mL], 30% [400 mL]). Collected fractions to give 7-chloro-8-iodo-3-(2,2,2-trifluoroethyl)imidazo[1,2-a]pyridine (261 mg, 73.7% yield) as a sticky yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.94 (d, J=7.3 Hz, 1H), 7.70 (s, 1H), 6.98 (d, J=7.3 Hz, 1H), 3.72 (q, J=9.9 Hz, 2H).

Provenance & Evidence